Propiconazole is a triazole fungicide previously shown to induce triglyceride accumulation in human liver HepaRG cells, potentially via activation of the Pregnane X Receptor (PXR). However, whether propiconazole can disrupt hepatic and whole-body metabolism in vivo is currently unknown. Therefore, we aimed to examine the metabolic effects of propiconazole in the context of metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, and insulin resistance. To this end, male C57BL/6J mice were fed a high-fat diet for 20 weeks. During the last 10 weeks, mice additionally received vehicle, 0.04, 30, or 100 mg/kg body weight (bw)/day propiconazole via oral gavage. High-dose propiconazole, but not low or intermediate dose, reduced body weight gain and adipose tissue weight in obese mice. Mice receiving high-dose propiconazole displayed improved glucose tolerance and reduced levels of plasma triglycerides and cholesterol. Propiconazole dose-dependently increased liver weight and triglyceride levels and at high dose caused signs of hepatic inflammation. RNA sequencing on the liver revealed that propiconazole mainly induced PXR target genes. At intermediate and high dose, propiconazole induced pathways related to cell-cell interactions and inflammation, while oxidative phosphorylation was repressed by propiconazole. Comparison of gene regulation in wildtype and PXR knockout primary hepatocytes as well as gene reporter assays confirmed the activation of PXR by propiconazole. All in all, our data underscore the capacity of propiconazole to activate PXR in the liver and thereby promote the development of hepatic steatosis in vivo.
- MeSH
- Diet, High-Fat * MeSH
- Insulin Resistance MeSH
- Liver drug effects metabolism pathology MeSH
- Disease Models, Animal MeSH
- Mice, Inbred C57BL * MeSH
- Mice MeSH
- Obesity * chemically induced MeSH
- Pregnane X Receptor * metabolism genetics MeSH
- Fungicides, Industrial * toxicity MeSH
- Triazoles * toxicity MeSH
- Triglycerides blood metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Fatty Liver * chemically induced MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: The distribution of time across physical activity, sedentary behaviors, and sleep appears to be essential for the management of obesity. However, the impact of reallocating time among these behaviors, collectively known as 24-h movement behaviors, remains underexplored. OBJECTIVE: This study examines the theoretical effects of reallocating time between 24-h movement behaviors on obesity indicators across different age groups. METHODS: We performed a pooled data meta-analysis of 9818 participants from 11 observational and experimental studies. To estimate the time spent in movement behaviors, we reprocessed and harmonized individual-level raw accelerometer-derived data. Isotemporal substitution models estimated theoretical changes in body mass index (BMI) and waist circumference (WC) associated with time reallocation between movement behaviors. We performed the analysis separately for children, adolescents, adults, and older adults. RESULTS: Even minor reallocations of 10 min led to significant changes in obesity indicators, with pronounced effects observed when 30 min were reallocated. The most substantial adverse effects on BMI and WC occurred when moderate-to-vigorous physical activity (MVPA) was reallocated to other movement behaviors. For 30-min reallocations, the largest increase in BMI (or BMI z-score for children) occurred when MVPA was reallocated to light-intensity physical activity (LPA) in children (0.26 units, 95% confidence interval [CI] 0.15, 0.37) and to sedentary behavior (SB) in adults (0.72 kg/m2, 95% CI 0.47, 0.96) and older adults (0.73 kg/m2, 95% CI 0.59, 0.87). The largest increase in WC was observed when MVPA was substituted with LPA in adults (2.66 cm, 95% CI 1.42, 3.90) and with SB in older adults (2.43 cm, 95% CI 2.07, 2.79). Conversely, the highest magnitude of the decrease in obesity indicators was observed when SB was substituted with MVPA. Specifically, substituting 30 min of SB with MVPA was associated with a decrease in BMI z-score by - 0.15 units (95% CI - 0.21, - 0.10) in children and lower BMI by - 0.56 kg/m2 (95% CI - 0.74, - 0.39) in adults and by - 0.52 kg/m2 (95% CI - 0.61, - 0.43) in older adults. Reallocating time away from sleep and LPA showed several significant changes but lacked a consistent pattern. While the predicted changes in obesity indicators were generally consistent across age groups, inconsistent findings were observed in adolescents, particularly for reallocations between MVPA and other behaviors. CONCLUSIONS: This investigation emphasizes the crucial role of MVPA in mitigating obesity risk across the lifespan, and the benefit of substituting SB with low-intensity movement behaviors. The distinct patterns observed in adolescents suggest a need for age-specific lifestyle interventions to effectively address obesity. Emphasizing manageable shifts, such as 10-min reallocations, could have significant public health implications, promoting sustainable lifestyle changes that accommodate individuals with diverse needs, including those with severe obesity.
- MeSH
- Accelerometry MeSH
- Time Factors MeSH
- Exercise * MeSH
- Child MeSH
- Adult MeSH
- Body Mass Index MeSH
- Obesity Management * methods MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Obesity * MeSH
- Waist Circumference MeSH
- Sedentary Behavior * MeSH
- Aged MeSH
- Sleep MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
Global obesity rates have risen dramatically, now exceeding deaths from starvation. Metabolic and bariatric surgery (MBS), initially for severe obesity (BMI ≥35 kg/m2), is performed globally over 500 000 times annually, offering significant metabolic benefits beyond weight loss. However, varying eligibility criteria globally impact patient care and healthcare resources. Updated in 2022, ASMBS and IFSO guidelines aim to standardise MBS indications, reflecting current understanding and emphasising comprehensive preoperative assessments. Yet, clinical variability persists, necessitating consensus-based recommendations. This modified Delphi study engaged 45 global experts to establish consensus on perioperative management in MBS. Experts selected from bariatric societies possessed expertise in MBS and participated in a two-round Delphi protocol. Consensus was achieved on 90 of 169 statements (53.3%), encompassing multidisciplinary team composition, patient selection criteria, preoperative testing, and referral pathways. The agreement highlighted the critical role of comprehensive preoperative assessments and the integration of healthcare professionals in MBS. These findings offer essential insights to standardise perioperative practices and advocate for evidence-based guidelines in MBS globally. The study underscores the need for unified protocols to optimise outcomes and guide future research in MBS.
- MeSH
- Bariatric Surgery * standards methods MeSH
- Delphi Technique * MeSH
- Consensus * MeSH
- Humans MeSH
- Obesity, Morbid surgery MeSH
- Preoperative Care * standards methods MeSH
- Patient Selection MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION AND OBJECTIVES: With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options. MATERIALS AND METHODS: This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months. RESULTS: Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009). CONCLUSIONS: Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis. GOV REGISTRATION: NCT04895943.
- MeSH
- Bariatric Surgery * MeSH
- Time Factors MeSH
- Equipment Design MeSH
- Adult MeSH
- Elasticity Imaging Techniques MeSH
- Weight Loss MeSH
- Liver Cirrhosis * etiology diagnostic imaging diagnosis MeSH
- Middle Aged MeSH
- Humans MeSH
- Non-alcoholic Fatty Liver Disease * diagnostic imaging diagnosis etiology MeSH
- Obesity * complications surgery diagnosis MeSH
- Pilot Projects MeSH
- Prospective Studies MeSH
- Treatment Outcome MeSH
- Gastric Balloon * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Clinical Trial MeSH
BACKGROUND: Plasma sulfur amino acids (SAAs), particularly cysteine, are associated with obesity. One proposed mechanism is the altered regulation of the stearoyl-CoA desaturase (SCD) enzyme. Changes in the SCD enzyme activity have been linked to obesity, as well as to plasma SAA concentrations. OBJECTIVE: This study aimed to investigate whether estimated SCD activity mediates the associations between plasma SAAs and measures of overall adiposity and specific fat depots. METHODS: We examined cross-sectional data from a subset of the Maastricht Study (n = 1129, 50.7% men, 56.7% with (pre)diabetes). Concentrations of methionine, total homocysteine, cystathionine, total cysteine (tCys), total glutathione (tGSH), and taurine were measured in fasting plasma. Outcomes included measures of overall, peripheral and central adiposity, and liver fat. SCD activity was estimated by ratios of serum fatty acids as SCD16 and SCD18 indices. The associations between plasma SAAs and measures of adiposity or liver fat were examined with multiple linear regression analysis. Multiple mediation analysis was used to investigate whether the significant associations were mediated by SCD16 and SCD18 indices. RESULTS: Plasma tCys was positively associated with all adiposity measures (β ranged from 0.15 to 0.30). SCD16 significantly mediated all associations (proportion mediated ranged from 5.1% to 9.7%). Inconsistent mediation effects were found for SCD18. Despite a significant inverse association of plasma tGSH with all adiposity measures (β ranged from -0.08 to -0.16), no significant mediation effect was found. CONCLUSIONS: Plasma tCys may promote excessive body fat accumulation via upregulation of SCD activity.
- MeSH
- Adiposity * MeSH
- Cysteine * blood MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Obesity blood MeSH
- Cross-Sectional Studies MeSH
- Stearoyl-CoA Desaturase * metabolism blood MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group. In a mega-analysis, we investigated the associations between BMI, diagnosis or medication and FA. Lower FA was associated with both BD and BMI in six white matter tracts, including the corpus callosum and thalamic radiation. Higher BMI or BD were uniquely associated with lower FA in three and six white matter tracts, respectively. People not receiving lithium treatment had a greater negative association between FA and BMI than people treated with lithium in the posterior thalamic radiation and sagittal stratum. In three tracts BMI accounted for 10.5 to 17% of the negative association between the number of medication classes other than lithium and FA. Both overweight/obesity and BD demonstrated lower FA in some of the same regions. People prescribed lithium had a weaker association between BMI and FA than people not on lithium. In contrast, greater weight contributed to the negative associations between medications and FA. Obesity may add to brain alterations in BD and may play a role in effects of medications on the brain.
- MeSH
- Anisotropy MeSH
- White Matter * pathology diagnostic imaging metabolism MeSH
- Bipolar Disorder * pathology metabolism MeSH
- Adult MeSH
- Body Mass Index MeSH
- Middle Aged MeSH
- Humans MeSH
- Brain pathology MeSH
- Obesity * pathology metabolism complications MeSH
- Gray Matter MeSH
- Diffusion Tensor Imaging methods MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Early life socioeconomic disadvantage and adverse experiences may lead to overeating, which is in turn associated with increased body mass index (BMI). However, recent evidence indicated that the association between childhood BMI and overeating might be bidirectional. This bidirectionality prompts the need for further investigation of early life predictors of BMI in childhood. OBJECTIVES: To longitudinally assess the directionality of the association between childhood BMI and perceived overeating and to investigate their antecedent early life predictors. METHODS: The sample included data from 5151 children from the ELSPAC study, collected between 18 months and 11 years of child age. The outcomes were child BMI and mother-reported overeating, assessed at the age of 3, 5, 7 and 11 years. Predictors included maternal BMI, maternal education, single parenthood, financial difficulties and adverse childhood experiences (ACEs) reported by parents and paediatricians. The random intercept cross-lagged panel model was applied. RESULTS: The mean child's BMI at age 3 was 15.59 kg/m2 and increased to 17.86 kg/m2 at age 11. The percentage of parent-reported overeating increased in the following period, from about 12% at age 3 to 17% at age 11. The results showed temporal stability in perceived overeating and BMI, with a bidirectional relationship strengthening over time. The child's BMI was associated with maternal BMI. Maternal BMI was positively associated with child-perceived overeating, but a stronger effect was found for ACEs. ACEs mediated the impact of maternal education, financial difficulties and single parenthood on overeating. CONCLUSIONS: We observed stable bidirectional associations between BMI and perceived overeating. The results indicated two main pathways: one linked to maternal BMI and early childhood BMI increase followed by perceived overeating and the second associated with ACEs mediating the effect of early childhood social factors on perceived overeating, leading to gradual BMI gain.
- MeSH
- Child MeSH
- Hyperphagia * psychology epidemiology MeSH
- Body Mass Index * MeSH
- Infant MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Mothers psychology statistics & numerical data MeSH
- Adverse Childhood Experiences * statistics & numerical data psychology MeSH
- Pediatric Obesity * epidemiology psychology MeSH
- Child, Preschool MeSH
- Socioeconomic Factors MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
230 stran : ilustrace ; 24 cm
Vysokoškolská učebnica, ktorá sa zameriava na liečbu extrémnej obezity. Určené aj odborníkom v praxi.
- Conspectus
- Patologie. Klinická medicína
- Učební osnovy. Vyučovací předměty. Učebnice
- NML Fields
- obezitologie
- NML Publication type
- učebnice vysokých škol
- Keywords
- tirzepatid,
- MeSH
- Glucagon-Like Peptide-1 Receptor Agonists pharmacology therapeutic use MeSH
- Diabetes Mellitus, Type 2 * drug therapy MeSH
- Hypoglycemic Agents pharmacology therapeutic use MeSH
- Clinical Studies as Topic MeSH
- Anti-Obesity Agents pharmacology therapeutic use MeSH
- Humans MeSH
- Obesity * drug therapy MeSH
- Gastric Inhibitory Polypeptide pharmacology therapeutic use MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
